Advancing Type 1 Diabetes Management: Integrating Novel Therapies, Technologies, and Adjunctive Approaches.

In type 1 diabetes, a condition that necessitates lifelong exogenous insulin replacement, there is heavy reliance on technology-assisted insulin delivery and glucose monitoring. Yet, people living with type 1 diabetes still face dysglycemia, weight gain, vascular complications, ketoacidosis and severe hypoglycemia, and psychological distress. Cardiovascular and kidney disease remain the leading causes of morbidity and mortality, yet traditional risk factors (smoking, hypertension, hyperlipidemia, obesity, hyperglycemia) incompletely explain this excess burden.

Altered brain function and structure in youth-onset type 2 diabetes.

Objective: Despite the aggressive clinical trajectory of youth-onset type 2 diabetes (Y-T2D) and consistent evidence of cognitive dysfunction and poor brain health in adults with T2D, the impact of Y-T2D on brain function and structure is understudied.

Design: This study aimed to characterize brain function and structure in a cross-sectional sample of young people with Y-T2D and compare these brain attributes to peers with obesity alone (OB) or healthy weight (HW) without T2D.

Methods: Brain structure and function were measured via magnetic resonance imaging.

Relationships among biological sex, body composition, and bone mineral density in young persons with and without diabetes.

Objectives: Bone mineral density (BMD) is influenced by factors including age, sex, body composition, and diabetes. However, data regarding these relationships in young individuals is limited. The objective of this study was to address this gap in the literature.

Unraveling Diabetic Kidney Disease: The Roles of Mitochondrial Dysfunction and Immunometabolism.

Mitochondria are essential for cellular energy production and are implicated in numerous diseases, including diabetic kidney disease (DKD). Current evidence indicates that mitochondrial dysfunction results in alterations in several metabolic pathways within kidney cells, thereby contributing to the progression of DKD. Furthermore, mitochondrial dysfunction can engender an inflammatory milieu, leading to the activation and recruitment of immune cells to the kidney tissue, potentially perturbing intrarenal metabolism.

Proteomic Analysis Uncovers Multiprotein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.

Key Points: Proteomics analyses identified seven proteins predictive of time to development of albuminuria among youth with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth cohort, 118 proteins predictive of time to development of hyperfiltration, and three proteins predictive of time to rapid eGFR decline. Seven proteins were predictive of all three outcomes (SEM4A, PSB3, dihydroxyphenylalanine decarboxylase, C1RL1, T132A, pyruvate carboxylase, and C1-esterase inhibitor) and have been implicated in immune regulatory mechanisms, metabolic dysregulation, proteostasis, and cellular signaling pathways. Elastic net Cox proportional hazards model identified distinct multiprotein signatures (38–68 proteins) of time to albuminuria, hyperfiltration, and rapid eGFR decline with concordance for models with clinical covariates and selected proteins between 0.

Pathophysiology and Treatment of Prediabetes and Type 2 Diabetes in Youth.

Youth-onset type 2 diabetes is a heterogeneous disease with increasing prevalence in relation to increased rates of obesity in children. It has genetic, epigenetic, social, and environmental determinants. Youth-onset type 2 diabetes is alarming given a rapidly progressive course compared with the course of adult-onset disease, early-onset vascular complications, and long-term exposure to hyperglycemia and associated complications.

Muscle mitochondrial function is impaired in adults with type 1 diabetes.

Aims: Type 1 diabetes has been associated with mitochondrial dysfunction. However, the mechanism of this dysfunction in adults remains unclear.

Methods: A secondary analysis was conducted using data from several clinical trials measuring in-vivo and ex-vivo mitochondrial function in adults with type 1 diabetes (n = 34, age 38.

Assessing Cognition in CKD Using the National Institutes of Health Toolbox.

Key Points: Participants with CKD had detectable cognitive deficits in fluid cognition, dexterity, and total cognition. Sex differences in cognition exist in people with CKD.

Background: CKD is largely an age-related clinical disorder with accelerated cognitive and cardiovascular aging.

Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes.

Objectives: Glycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D.

Methods: Glomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.

Minireview: Understanding and targeting inflammatory, hemodynamic and injury markers for cardiorenal protection in type 1 diabetes.

The coexistence of cardiovascular disease (CVD) and diabetic kidney disease (DKD) is common in people with type 1 diabetes (T1D) and is strongly associated with an increased risk of morbidity and mortality. Hence, it is imperative to explore robust tools that can accurately reflect the development and progression of cardiorenal complications. Several cardiovascular and kidney biomarkers have been identified to detect at-risk individuals with T1D.

Pharmacological management of youth with type 2 diabetes and diabetic kidney disease: a comprehensive review of current treatments and future directions.

Introduction: Diabetic kidney disease (DKD) is a leading cause of mortality in people with type 2 diabetes (T2D), and over 50% of individuals with youth-onset T2D will develop DKD as a young adult. Diagnosis of early-onset DKD remains a challenge in young persons with T2D secondary to a lack of available biomarkers for early DKD, while the injuries may still be reversible. Furthermore, multiple barriers exist to initiate timely prevention and treatment strategies for DKD, including a lack of Food and Drug Administration approval of medications in pediatrics; provider comfort with medication prescription, titration, and monitoring; and medication adherence.

Triglyceride content of lipoprotein subclasses and kidney hemodynamic function and injury in adolescents with type 1 diabetes.

Aims: Elevated triglycerides (TG) are associated with development and progression of kidney disease, and TG distributions across lipoprotein subclasses predict kidney dysfunction in adults with type 1 diabetes (T1D). Little is known regarding these relationships in youth.

Methods: In this single center study conducted from October 2018-2019, lipid constituents from lipoprotein subclasses were quantified by targeted nuclear magnetic resonance spectroscopy.

Youth versus adult-onset type 2 diabetic kidney disease: Insights into currently known structural differences and the potential underlying mechanisms.

Type 2 diabetes (T2D) is a global health pandemic with significant humanitarian, economic, and societal implications, particularly for youth and young adults who are experiencing an exponential rise in incident disease. Youth-onset T2D has a more aggressive phenotype than adult-onset T2D, and this translates to important differences in rates of progression of diabetic kidney disease (DKD). We hypothesize that youth-onset DKD due to T2D may exhibit morphometric, metabolic, and molecular characteristics that are distinct from adult-onset T2D and develop secondary to inherent differences in renal energy expenditure and substrate metabolism, resulting in a central metabolic imbalance.

Continuous Glucose Monitor, Insulin Pump, and Automated Insulin Delivery Therapies for Type 1 Diabetes: An Update on Potential for Cardiovascular Benefits.

Purpose Of Review: The incidence of type 1 diabetes (T1D) is rising in all age groups. T1D is associated with chronic microvascular and macrovascular complications but improving glycemic trends can delay the onset and slow the progression of these complications. Utilization of technological devices for diabetes management, such as continuous glucose monitors (CGM) and insulin pumps, is increasing, and these devices are associated with improvements in glycemic trends.

Coffee Consumption May Mitigate the Risk for Acute Kidney Injury: Results From the Atherosclerosis Risk in Communities Study.

Introduction: Coffee is one of the most frequently consumed beverages worldwide and has been found to have a wide assortment of health benefits. Although habitual coffee consumption is associated with a lower incidence of chronic kidney disease, an association between coffee and acute kidney injury (AKI) has not yet been revealed.

Methods: In the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort study of 14,207 adults aged 45 to 64 years, coffee consumption (cups/d) was assessed at a single visit via food frequency questionnaires and compared with incident AKI defined by hospitalization with an AKI-related International Classification of Diseases code.

Aminoaciduria and metabolic dysregulation during diabetic ketoacidosis: Results from the diabetic kidney alarm (DKA) study.

Objective: We examined changes in the excretion of various amino acids and in glycolysis and ketogenesis-related metabolites, during and after diabetic ketoacidosis (DKA) diagnosis, in youth with known or new onset type 1 diabetes (T1D).

Methods: Urine samples were collected from 40 youth with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.

Relationship between biomarkers of tubular injury and intrarenal hemodynamic dysfunction in youth with type 1 diabetes.

Background: Early identification of youth with type 1 diabetes (T1D) at risk for diabetic kidney disease may improve clinical outcomes. We examined the cross-sectional relationship between kidney biomarkers neutrophil gelatinase-associated lipocalin (NGAL), copeptin, interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), chitinase-3-like protein-1 (YKL-40), and monocyte chemoattractant protein-1 (MCP-1) and intrarenal hemodynamic function in adolescents with T1D.

Methods: Urine albumin-to-creatinine ratio (UACR), renal vascular resistance (RVR), glomerular filtration rate (GFR), intraglomerular pressure (P), efferent arteriole resistance (R), afferent arteriolar resistance (R), and renal plasma flow (RPF), and the above indicated biomarkers were assessed in youth aged 12-21 years with and without T1D of < 10 years duration.

Mechanisms of Cardiorenal Protection of Glucagon-Like Peptide-1 Receptor Agonists.

The worldwide prevalence of type 2 diabetes (T2D) is steadily increasing, and it remains a challenging public health problem for populations in both developing and developed countries around the world. Despite the recent advances in novel antidiabetic agents, diabetic kidney disease and cardiovascular disease remain the leading causes of morbidity and mortality in T2D. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), incretin hormones that stimulate postprandial insulin secretion, serve as a promising avenue for treatment of T2D as they result in a variety of antihyperglycemic effects including increased endogenous insulin secretion, decreased gluconeogenesis, inhibition of pancreatic α-cell glucagon production, decreased pancreatic β-cell apoptosis, and increased β-cell proliferation.

A Pilot Study of the Safety and Efficacy of Alkali Therapy on Vascular Function in Kidney Transplant Recipients.

Introduction: Metabolic acidosis is associated with cardiovascular events, graft function, and mortality in kidney transplant recipients (KTRs). We examined the effect of alkali therapy on vascular endothelial function in KTRs.

Methods: We performed an 18-week, randomized, double-blind, placebo-controlled crossover pilot study examining the effect of sodium bicarbonate therapy versus placebo on vascular function in 20 adult KTRs at least 1 year from transplant with an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.